摘要
目的 从蛋白质水平研究转化生长因子 (TGFβ1)在梗阻性肾病中所起的作用及血管紧张素转化酶抑制剂 -西那普利 (Cilazapril)对其表达的影响。方法 除对照组 (C组 )外的所有成年SD大鼠均接受单侧输尿管结扎术 (UUO) ,术前 2 4h起治疗组 (A组 )每日予Cilazapril(10mg/kgday)灌胃 ,B组与C组则予相同剂量的生理盐水灌胃 ,共 15d。采用图象分析仪检测结扎侧肾 (OK)小管肾间质的面积及纤维连接蛋白 (FN)和I型胶原的含量 ,增殖细胞核抗原 (PCNA)染色计算增殖细胞数。TGFβ1则利用免疫组化及Westernblot杂交两种方法检测。结果 C组肾间质的TGFβ1蛋白几乎不表达 ,而B组表达较强 ,同时B组的肾间质面积、FN、I型胶原水平及增殖细胞数均显著增加 (P <0 .0 5 )。而A组使用Cilazapril后可使其TGFβ1的蛋白表达下降到B组的 1/4.6 1,肾间质面积及FN、I型胶原含量也显著减少 (P <0 .0 5 )。结论 TGFβ1蛋白水平表达增加很可能是梗阻性肾病的重要致病因素之一 ,而Cilazapril由于能使其表达减少从而对梗阻侧肾脏起到重要的保护作用。
Objective To evaluate the role of transforming growth factor β1(TGFβ1)in obstructive nephropathy and the effect of an angiotension converting enzyme (ACE) inhibitor,cilazapril. Methods All the adult SD rats received unilateral ureteral obstruction(UUO) except Group C. Cilazapril(10mg·kg -1 ·d -1 ) or the same amount of water was administered by gavage beginning 24 hours before UUO and continued through fifteen days after UUO. The volume of tubulointerstitium in the obstructed kidney (OK)was examined by an image analyzer. Fiberonectin(FN) and collagen type I (collagen I)protein deposition in OK were examined histogically using specific antibodies. The proliferating cells were calculated with PCNA stain. We also examined the protein levels of TGFβ1 by immunochemistry and western blot analysis. Results TGFβ1 almost didn't express in group C, but it could be found evidently in group A. Meanwhile in group B, the volume of the tubulointerestitium ,proliferating cells, FN and collagen I increased much higher than any group(P<0.05).But cilazapril could decrease its TGFβ1 expression by 1/4, proliferating cells and FN as well as collagen I were also greatly reduced (P<0.05).Conclusion This study indicates that TGFβ1 has a major role in the pathogenesis of the tubulointerestitium fibrosis of obstruction nephropathy. While cilazapril achieved its protection probably mediated by the decreased levels of TGFβ1.
出处
《上海医学》
CAS
CSCD
北大核心
2001年第7期424-427,F002,共5页
Shanghai Medical Journal